Predictors of osteoporotic fracture in postmenopausal women: a meta-analysis.

Osteoporosis affects more than 200 million women worldwide, with postmenopausal women being particularly susceptible to this condition and its severe sequelae disproportionately, such as osteoporotic fractures. To date, the current focus has been more on symptomatic treatment, rather than preventive measures. To address this, we performed a meta-analysis aiming to identify potential predictors of osteoporotic fractures in postmenopausal women, with the ultimate goal of identifying high-risk patients and exploring potential therapeutic approaches. We searched Embase, MEDLINE and Cochrane with search terms (postmenopausal AND fracture) AND ("risk factor" OR "predictive factor") in May 2022 for cohort and case-control studies on the predictors of osteoporotic fracture in postmenopausal women. Ten studies with 1,287,021 postmenopausal women were found eligible for analyses, in which the sample size ranged from 311 to 1,272,115. The surveyed date spanned from 1993 to 2021. Our results suggested that age, BMI, senior high school and above, parity ≥ 3, history of hypertension, history of diabetes mellitus, history of alcohol intake, age at menarche ≥ 15, age at menopause < 40, age at menopause > 50, estrogen use and vitamin D supplements were significantly associated with osteoporotic fracture in postmenopausal women. Our findings facilitate the early prediction of osteoporotic fracture in postmenopausal women and may contribute to potential therapeutic approaches. By focusing on preventive strategies and identifying high-risk individuals, we can work toward reducing the burden of osteoporosis-related fractures in this vulnerable population.

A new insight of immunosuppressive microenvironment in osteosarcoma lung metastasis.

The lung is the primary organ for the metastasis of osteosarcoma. Although the application of neoadjuvant chemotherapy and surgery has remarkably improved the survival rate of patients with osteosarcoma, prognosis is still poor for those patients with metastasis. In this study, we performed further bioinformatics analysis on single-cell RNA sequencing (scRNA-seq) data published before, containing 75,317 cells from two osteosarcoma lung metastasis and five normal lung tissues. First, we classified 17 clusters, including macrophages, T cells, endothelial cells, and so on, indicating highly intratumoral heterogeneity in osteosarcoma lung metastasis. Next, we found macrophages in osteosarcoma lung metastasis did not have significant M1 or M2 polarizations. Then, we identified that T cells occupied the most abundant among all cell clusters, and found CD8+ T cells exhibited a low expression level of immune checkpoints in osteosarcoma lung metastasis. What is more, we identified C2_Malignant cells, and found CD63 might play vital roles in determining the infiltration of T cells and malignant cells in conventional-type osteosarcoma lung metastasis. Finally, we unveiled C1_Therapeutic cluster, a subcluster of malignant cells, was sensitive to oxfendazole and mevastatin, and the potential hydrogen-bond position and binding energy of oxfendazole-KIAA0907 and mevastatin-KIAA0907 were unveiled, respectively. Our results highlighted the power of scRNA-seq technique in identifying the complex tumor microenvironment of osteosarcoma lung metastasis, making it possible to devise precision therapeutic approaches.

Comprehensive analysis of protein phosphatase 1 regulatory inhibitor subunit 14B, a molecule related to tumorigenesis, poor prognosis, and immune cell infiltration in lung adenocarcinoma.

OBJECTIVE: To explore the relationship between Protein Phosphatase 1 Regulatory Inhibitor Subunit 14B (PPP1R14B) and the occurrence of lung adenocarcinoma (LUAD). METHOD: PPP1R14B expression was investigated using various databases, and its molecular functions and pathways were evaluated using Gene Set Variation Analysis (GSVA) and Gene Set Enrichment Analysis (GSEA). Then, the correlation between tumor mutations and PPP1R14B expression was analyzed. Furthermore, the regulation network and expression pathway axes of PPP1R14B were constructed. The correlation analysis between PPP1R14B and immune cell infiltration was performed using deconvolution algorithm analysis and the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical (IHC) staining of the clinical samples were used for expression validation. RESULTS: PPP1R14B showed high expression in tumor tissue. PPP1R14B was associated with T and N stages and poor prognosis and was linked to the cell cycle, DNA repair, and low immune response. High PPP1R14B expression was associated with high tumor mutation rates. The upstream and downstream genes of PPP1R14B were identified, along with the construction of a protein-protein interaction network (PPI network) and the expression pathway axes of PPP1R14B. PPP1R14B expression was associated with poor immune cell infiltration and a negative correlation between PPP1R14B and mast cell and eosinophil infiltration. CONCLUSION: This study reveals high PPP1R14B expression in LUAD, its contribution to poor prognosis, molecular function, biological pathways, and impact on immune cell infiltration, and provides great insight into the role of PPP1R14B in LUAD tumorigenesis.

Trends of denosumab-related publications in web of science.

Denosumab is a human monoclonal antibody that targets nuclear factor-kappa B ligand and is highly effective in blocking bone resorption. Bibliometrics can intuitively show the research development process, research status, research hotspots and development trend of a certain topic for researchers. This study assessed the course of research and development for denosumab in terms of publications over the past 2 decades. Web of Science databases were searched to identify publications related to research on denosumab from January 1, 2005 to December 31, 2022. The VOS Viewer software (version 1.6.17) and Bibliometrix package in R (version 4.1.3) were used in this study. There were 5119 denosumab-related publications during this period. The total number of citations of denosumab-related publications reached 94917. The most articles were published in the field of Endocrinology Metabolism. As an international language, English remains the most popular language for writing papers. Five of the top ten institutions originated in the USA. Through the VOS Viewer analysis, we found that the relationships between Amgen Inc. with its collaborations were grouped into 4 clusters, the USA was the mainland for research and development on denosumab, closely collaborating with many other countries, such as Canada, Japan, England, and China. Wagman RB from USA was the most prolific author with 119 publications. The journal with the most publications was Osteoporosis International (481 publications). The most cited article was "Denosumab for Prevention of Fractures in Postmenopausal Women with Osteoporosis" with 2053 citations. The clinical trial comprised 6 of the 10 most frequently cited publications, and the rest consisted of reviews. The most frequent keywords for publications since January 1, 2014 were "prevention" and "management," indicating that a number of prevention and management measures have been developed to regulate the use of denosumab in treating osteoporosis. Our research provided a comprehensive review of denosumab-related publications, suggesting that the development of denosumab is a long process and numerous clinical trials have been conducted before applications in clinical settings.

Analysis of scRNA-seq and bulk RNA-seq demonstrates the effects of EVI2B or CD361 on CD8+ T cells in osteosarcoma.

Osteosarcoma (OS) is a common primary malignant tumor of the bone in children and adolescents. The five-year survival rate is estimated to be ~70% based on the currently available treatment modalities. It is well known that tumor-infiltrating immune cells (TIICs) that are the most important components in the tumor microenvironment can exert a killing effect on tumor cells. Therefore, in the present study, 85 RNA-sequencing OS samples were categorized into high- and low-immune score groups with ESTIAMATE. Based on the immune score groups, 474 differentially expressed genes (DEGs) were acquired using the LIMMA package of R language. Subsequently, 86 DEGs were taken through univariate COX regression analysis, of which 14 were screened out by least absolute shrinkage and selection operator regression analysis. Furthermore, multivariate COX regression analysis was performed to obtain 4 DEGs. Finally, ecotropic virus integration site 2B (EVI2B) or CD361 gene was screened out via Kaplan-Meier analysis. In addition, CIBERSORT algorithm was used to evaluate the proportion of 22 kinds of TIICs in OS. Correlation analysis revealed that the high expression level of EVI2B can elevate the infiltrated proportion of CD8+ T cells. Moreover, analysis of single cell RNA-sequencing transcriptome datasets and immunohistochemical staining uncovered that EVI2B was mainly expressed on CD8+ T cells and that EVI2B could promote the expression of granzyme A and K of CD8+ T cells to exhibit a potent killing effect on tumor cells. Therefore, EVI2B was identified as a protective immune-related gene and contributed to good prognosis in OS patients.

Corrigendum: Single-cell transcriptomics reveals the complexity of the tumor microenvironment of treatment-naive osteosarcoma.

[This corrects the article DOI: 10.3389/fonc.2021.709210.].

Aneurysmal bone cyst secondary to giant cell tumor of the extremities: a case series of 30 patients.

The purpose was to investigate the clinical features, diagnosis, treatment, and prognosis of aneurysmal bone cyst (ABC) secondary to giant cell tumors (GCT) of the extremities. Data from patients with ABC secondary to GCT of the extremities were obtained from the medical records. Clinical features, imaging findings, pathologic diagnosis, surgical methods, and prognosis were analyzed. The median age of the patients was 33 years (range 15 to 52 years) and 83.3 percent were between 20 to 40 years. The lesions were mainly located in the proximal tibia and distal femur, accounting for 63.3% (19/30). 21 patients were treated with curettage, and 9 with tumor resection. The recurrence rates of the curettage group and resection group were 52.4% and 11.1% respectively. However, the average postoperative (Musculoskeletal Tumor Society) MSTS score were 28.6±1.2 post-curettage, and 25.0±0.5 post-resection, with a significant difference between the 2 groups (P<0.01). In these relapsed patients, 10 underwent a second curettage, while 2 cases underwent a resection and there was no postoperative re-recurrence in both groups. A comprehensive analysis should be performed when making the diagnosis of ABC secondary to GCT. Although the recurrence rate is higher, curettage is still the optimal method for satisfactory joint function. If recurrence occurs after the first curettage, a second curettage should be performed.

ATG16L1 is a Potential Prognostic Biomarker and Immune Signature for Osteosarcoma: A Study Based on Bulk RNA and Single-Cell RNA-Sequencing.

BACKGROUND: Osteosarcoma is a common solid malignancy of the bone in children and adolescents, and its metastasis and recurrence are the principal causes of poor treatment outcomes. METHODS: Autophagy-related genes were used to cluster osteosarcoma patients by consensus clustering analysis using the GSE21257 database. Differentially expressed genes (DEGs) were identified by limma package. Multiple-gene risk signature was constructed using least absolute shrinkage and selection operator (LASSO) analysis and Cox regression analyses. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to determine gene expression levels. Then, single-cell RNA-sequencing dataset GSE152048 were used to identify the correlation between the DEGs and effector molecules expressed in specific tumor-infiltrating immune cells. RESULTS: Two clusters were identified in the consensus clustering analysis, which were confirmed by principal component analysis. Limma analysis revealed that 15 genes were related, and 9 genes were screened using protein-protein interaction network and LASSO regression analysis. Cox regression analyses identified 5 genes. Combined with survival analysis, only the autophagy related 16 like 1 gene (ATG16L1) was significant. The results of qRT-PCR showed low expression levels of ATG16L1 in tumor cells group. Immune infiltration analysis revealed significantly lower expression of CD8+ T cells in the high ATG16L1 gene expression group. ScRNA-seq revealed that in the ATG16L1+ CD8 + T cell group, the expression of GZMB was lower, whereas the expression of ITGA1 was higher. These results showed that ATG16L1 is an immune-related gene, which is associated with poor prognosis in patients with osteosarcoma. CONCLUSION: ATG16L1 is a potential prognostic biomarker and immune signature and may be a therapeutic target for osteosarcoma.

STAT3 and SPI1, may lead to the immune system dysregulation and heterotopic ossification in ankylosing spondylitis.

OBJECTIVE: This study was aimed to identify the biomarkers for diagnosis and reveal the immune microenvironment changes in ankylosing spondylitis (AS). METHODS: GSE73754 was downloaded for the co-expression network construction and immune cell analyses. Flow cytometric analysis was performed to validate the results of bioinformatics analysis. Gene set enrichment analysis (GSEA) was performed to investigate the potential biological characteristic between different phenotypes. Pearson correlation analysis between the hub genes and the xCell score of immune cell types was performed. RESULTS: Signal transducer and activator of transcription 3 (STAT3) and Spi-1 proto-oncogene (SPI1) was identified as the hub genes in the datasets GSE73754. And the t-test showed that the expression level of STAT3 and SPI1 in the GSE73754 was significantly higher in AS and human leukocyte antigen (HLA)-B27(+) groups. Flow cytometric analysis showed that natural killer T cells (NKT) cells were upregulated, while Th1 cells were down-regulated in AS, which was consistent with the results obtained from bioinformatics analysis. STAT3 and SPI1 was correlated with the NKT cells and Th1 cells. CONCLUSION: STAT3 and SPI1 may be a key cytokine receptor in disease progression in AS.

STAT1 and CXCL10 involve in M1 macrophage polarization that may affect osteolysis and bone remodeling in extrapulmonary tuberculosis.

OBJECTIVE: This study was aimed to reveal the molecular mechanism of bone destruction due to macrophage polarization leading to during extrapulmonary tuberculosis (EPTB) infection. METHODS: The dataset GSE83456 was downloaded from the GEO database, and the xCell tool was used to obtain the 64 types of immune cells. The flow cytometry was performed to identified the differences between M1 and M2 macrophages between EPTB and the healthy controls (HCs). The enrichment analyses were performed on the differentially expressed genes (DEGs) and their functionally related modules. The hub genes were screened out, and their relationships with EPTB and the immune cell subtypes were further analyzed. RESULTS: The flow cytometric analysis validated this hypothesis of M1-macrophage polarization correlated with the pathogenesis of EPTB. Of the obtained 103 DEGs, 97 genes were upregulated, and 6 genes were downregulated. The GO and KEGG pathway analyses showed that the DEGs were particularly involved in the immune-related processes. The hub genes (STAT1 and CXCL10) might be involved in M1-macrophage polarization and correlated with the pathogenesis of EPTB. STAT1 and CXCL10 could also behave as biomarkers for EPTB. CONCLUSION: STAT1 and CXCL10 were involved in the M1-macrophage polarization and correlated with the pathogenesis of EPTB. Besides, both of them could also behave as biomarkers for EPTB diagnosis and provide the required clues for targeted therapy in the future.

Epithelial-mesenchymal transition interaction with CD8+ T cell, dendritic cell and immune checkpoints in the development of melanoma.

BACKGROUND: Melanoma is fatal cancer originating from melanocytes, whose high metastatic potential leads to an extremely poor prognosis. OBJECTIVE: This study aimed to reveal the relationship among EMT, TIICs, and immune checkpoints in melanoma. METHODS: Gene expression data and clinical data of melanoma were downloaded from TCGA, UCSC Xena and GEO databases. EMT-related DEGs were detected for risk score calculation. "ESTIMATE" and "xCell" were used for estimating TIICs and obtaining 64 immune cell subtypes, respectively. Moreover, we evaluated the relationship between the risk score and immune cell subtypes and immune checkpoints. RESULTS: Seven EMT-related genes were selected to establish a risk scoring system because of their integrated prognostic relevance. The results of GSEA revealed that most of the gene sets focused on immune-related pathways in the low-risk score group. The risk score was significantly correlated with the xCell score of some TIICs, which significantly affected the prognosis of melanoma. Patients with a low-risk score may be associated with a better response to ICI therapy. CONCLUSION: The individualized risk score could effectively conduct risk stratification, overall survival prediction, ICI therapy prediction, and TME judgment for patients with melanoma, which would be conducive to patients' precise treatment.

Ferroptosis-related gene SOCS1, a marker for tuberculosis diagnosis and treatment, involves in macrophage polarization and facilitates bone destruction in tuberculosis.

This study was aimed to reveal the role of ferroptosis in tuberculosis infection. To elucidate the ferroptosis-related DEGs, GEO datasets associated with tuberculosis infection were downloaded. The two external validation GEO datasets were exploited for subsequent verification of the ferroptosis-related DEGs. We further evaluated the correlation among the ferroptosis-related DEGs, therapeutic effects, and drug resistance. Finally, we tried to reveal the engagement of the ferroptosis-related DEGs in bone destruction during TB infection. The present study identified SOCS1 as the only ferroptosis-related DEGs. Compared to the non-TB patients, up-regulation of SOCS1 was evident in the TB patients. After receiving standard anti-TB treatment, significant down-regulation of SOCS1 confirmed its acceptance as the marker for therapeutic efficacy. The involvement of SOCS1 has also been suggested in the regulation of the micro immune environment in TB. Furthermore, SOCS1 might play an important role in causing bone destruction during TB infection. FRGs-SOCS1 may be the key gene involved in the pathogenesis and progression of TB infection.

Platelet-to-Lymphocyte Ratio as an Independent Factor Was Associated With the Severity of Ankylosing Spondylitis.

The study was aimed to determine the association of the platelet-lymphocyte ratio (PLR) with the disease activity of ankylosing spondylitis (AS). A total of 275 patients, including 180 AS patients and 95 non-AS patients, participated in the study. We assessed a full blood count for each participant. Platelet to monocyte ratio (PMR), monocytes to lymphocyte ratio (MLR), monocyte to neutrophil ratio (MNR), platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), and platelet to neutrophil ratio (PNR) were calculated. LASSO and logistic regression analyses were performed to establish the nomogram. Receiver operating characteristic (ROC) analysis was performed to evaluate the clinical value of the nomogram. We constructed a novel nomogram, which incorporated easily accessible clinical characteristics like sex, PLR, WBC, EOS, and ESR for AS diagnosis. The AUC value of this nomogram was 0.806; also, the calibration curves indicated a satisfactory agreement between nomogram prediction and actual probabilities. Furthermore, PLR was positively correlated with the severity of AS. PLR was identified as an independent factor for the diagnosis of AS and was associated with the severity of AS.

Single-Cell RNA Sequencing Reveals the Migration of Osteoclasts in Giant Cell Tumor of Bone.

Giant cell tumor of bone (GCTB) is benign tumor that can cause significant osteolysis and bone destruction at the epiphysis of long bones. Osteoclasts are thought to be highly associated with osteolysis in GCTB. However, the migration of osteoclasts in GCTB remains unclear. A deeper understanding of the complex tumor microenvironment is required in order to delineate the migration of osteoclasts in GCTB. In this study, samples were isolated from one patient diagnosed with GCTB. Single-cell RNA sequencing (scRNA-seq) was used to detect the heterogeneity of GCTB. Multiplex immunofluorescence staining was used to evaluate the cell subtypes identified by scRNA-seq. A total of 8,033 cells were obtained from one patient diagnosed with GCTB, which were divided into eight major cell types as depicted by a single-cell transcriptional map. The osteoclasts were divided into three subsets, and their differentiation trajectory and migration status were further analyzed. Osteoclast migration may be regulated via a series of genes associated with cell migration. Furthermore, four signaling pathways (RANKL, PARs, CD137 and SMEA3 signaling pathway) were found to be highly associated with osteoclast migration. This comprehensive single-cell transcriptome analysis of GCTB identified a series of genes associated with cell migration as well as four major signaling pathways that were highly related to the migration of osteoclasts in GCTB. Our findings broaden the understanding of GCTB bionetworks and provides a theoretical basis for anti-osteolysis therapy against GCTB in the future.

TYROBP, TLR4 and ITGAM regulated macrophages polarization and immune checkpoints expression in osteosarcoma.

We established a relationship among the immune-related genes, tumor-infiltrating immune cells (TIICs), and immune checkpoints in patients with osteosarcoma. The gene expression data for osteosarcoma were downloaded from UCSC Xena and GEO database. Immune-related differentially expressed genes (DEGs) were detected to calculate the risk score. "Estimate" was used for immune infiltrating estimation and "xCell" was used to obtain 64 immune cell subtypes. Furthermore, the relationship among the risk scores, immune cell subtypes, and immune checkpoints was evaluated. The three immune-related genes (TYROBP, TLR4, and ITGAM) were selected to establish a risk scoring system based on their integrated prognostic relevance. The GSEA results for the Hallmark and KEGG pathways revealed that the low-risk score group exhibited the most gene sets that were related to immune-related pathways. The risk score significantly correlated with the xCell score of macrophages, M1 macrophages, and M2 macrophages, which significantly affected the prognosis of osteosarcoma. Thus, patients with low-risk scores showed better results with the immune checkpoints inhibitor therapy. A three immune-related, gene-based risk model can regulate macrophage activation and predict the treatment outcomes the survival rate in osteosarcoma.

Single-Cell Transcriptomics Reveals the Complexity of the Tumor Microenvironment of Treatment-Naive Osteosarcoma.

Osteosarcoma (OS), which occurs most commonly in adolescents, is associated with a high degree of malignancy and poor prognosis. In order to develop an accurate treatment for OS, a deeper understanding of its complex tumor microenvironment (TME) is required. In the present study, tissues were isolated from six patients with OS, and then subjected to single-cell RNA sequencing (scRNA-seq) using a 10× Genomics platform. Multiplex immunofluorescence staining was subsequently used to validate the subsets identified by scRNA-seq. ScRNA-seq of six patients with OS was performed prior to neoadjuvant chemotherapy, and data were obtained on 29,278 cells. A total of nine major cell types were identified, and the single-cell transcriptional map of OS was subsequently revealed. Identified osteoblastic OS cells were divided into five subsets, and the subsets of those osteoblastic OS cells with significant prognostic correlation were determined using a deconvolution algorithm. Thereby, different transcription patterns in the cellular subtypes of osteoblastic OS cells were reported, and key transcription factors associated with survival prognosis were identified. Furthermore, the regulation of osteolysis by osteoblastic OS cells via receptor activator of nuclear factor kappa-B ligand was revealed. Furthermore, the role of osteoblastic OS cells in regulating angiogenesis through vascular endothelial growth factor-A was revealed. C3_TXNIP+ macrophages and C5_IFIT1+ macrophages were found to regulate regulatory T cells and participate in CD8+ T cell exhaustion, illustrating the possibility of immunotherapy that could target CD8+ T cells and macrophages. Our findings here show that the role of C1_osteoblastic OS cells in OS is to promote osteolysis and angiogenesis, and this is associated with survival prognosis. In addition, T cell depletion is an important feature of OS. More importantly, the present study provided a valuable resource for the in-depth study of the heterogeneity of the OS TME.

Immune status changing helps diagnose osteoarticular tuberculosis.

OBJECTIVE: This study is aimed to develop a new nomogram for the clinical diagnosis of osteoarticular tuberculosis (TB). METHODS: xCell score estimation to obtained the immune cell type abundance scores. We downloaded the expression profile of GSE83456 from GEO and proceed xCell score estimation. The routine blood examinations of 326 patients were collected for further validation. We analyzed univariate and multivariate logistic regression to identified independent predicted factor for developing the nomogram. The performance of the nomogram was assessed using the receiver operating characteristic (ROC) curves. The correlation of ESR with lymphocytes, monocytes, and ML ratio was performed and visualized in osteoarticular TB patients. RESULTS: Compared with the healthy control group in the dataset GSE83456, the xCell score of basophils, monocytes, neutrophils, and platelets was higher, while lymphoid was lower in the EPTB group. The clinical data showed that the cell count of monocytes were much higher, while the cell counts of lymphocytes were lower in the osteoarticular TB group. AUCs of the nomogram was 0.798 for the dataset GSE83456, and 0.737 for the clinical data. We identified the ML ratio, BMI, and ESR as the independent predictive factors for osteoarticular TB diagnosis and constructed a nomogram for the clinical diagnosis of osteoarticular TB. AUCs of this nomogram was 0.843. CONCLUSIONS: We demonstrated a significant change between the ML ratio of the EPTB and non-TB patients. Moreover, we constructed a nomogram for the clinical diagnosis of the osteoarticular TB diagnosis, which works satisfactorily.

A Retrospective Study of Factors Associated with Restoration of Thoracic Kyphosis in 43 Patients with Adolescent Idiopathic Scoliosis with Lenke Type 1 Curvature.

BACKGROUND This retrospective study aimed to identify the factors associated with successful surgical correction of thoracic kyphosis (TK) in 43 patients with adolescent idiopathic scoliosis (AIS) with Lenke type 1 curvature, in which the major curve with the largest Cobb angle was mainly in the thoracic region. MATERIAL AND METHODS We collected data from patients with Lenke 1 AIS. The following parameters were measured: Cobb angle, side-bending Cobb angle, cervical lordosis (CL), TK, lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), the sagittal vertical axis (SVA), the center of a C7 plumb line to the center sacral vertical line (C7-CSVL), correction rate, Ponte osteotomy, flexibility, and screw density. Univariate analysis and multivariate logistic regression analyses were performed. RESULTS Among the 43 cases analyzed, the mean postoperative Cobb angle at the last follow-up, C7-CSVL, SVA, CL, TK, LL, PI, SS, and PT were respectively 21.33±9.47°, 10.41±8.45 mm, 19.68±14.33 mm, 16.19±7.45°, 23.12±7.45°, 50.33±11.37°, 49.70±9.83°, 39.42±8.11°, and 10.16±6.63°. Univariate analysis suggested that preoperative TK, preoperative LL, and Ponte osteotomy were statistically significant (P<0.05), and multivariate analysis suggested that preoperative LL and Ponte osteotomy were statistically significant (P<0.05). CONCLUSIONS The results of this study demonstrated that preoperative TK, preoperative LL, and Ponte osteotomy were related factors for maintaining normal TK. Multivariate analysis suggested that preoperative LL and the use of Ponte osteotomy with full-thickness segmental resection of the spinal posterior column resulted in the successful surgical correction of TK in patients with AIS with Lenke type 1 curvature.

Establishment of immune prognostic signature and analysis of prospective molecular mechanisms in childhood osteosarcoma patients.

BACKGROUND: In pediatric tumors, immunotherapy exhibits less toxicity than chemotherapy and radiation. The current study aims to identify potential immune targets in immune-related genes of C-C motif chemokine ligand genes (CCLs) and C-C motif chemokine receptors (CCRs) in childhood osteosarcoma (OS) and to explore the underlying molecular mechanisms of childhood OS. METHODS: Firstly, we identified immune-related genes in CCLs and CCRs, these genes were used for functional annotation and interaction analysis. Then, the prognostic value of these genes was evaluated using Kaplan-Meier analysis and multivariate COX regression model. And the potential relationship between risk score and immune infiltrating cells was identified. Finally, gene set enrichment analysis was used to determine the underlying molecular mechanism of OS. Immune-related genes in CCLs and CCRs are inextricably linked. RESULTS: The results of survival analysis of these genes show that CCL5, CCL8, CCR4, and CCR5 are significantly associated with the prognosis of childhood OS. The combined effect survival analysis shows that the co-high expression of these 4 genes has a good prognosis for childhood OS. A prognostic signature model was constructed based on the 4 genes mentioned above, and the result of time-dependent receiver operating characteristic curves showed that this model was a good predictor of childhood OS 3- and 5-year prognosis. In addition, the risk score of the constructed prognostic signature model was closely related to immune infiltration. We also found that CCL5, CCL8, and CCR5 may affect the prognosis of OS through complex regulation among Toll-like receptor signaling pathway, mitogen-activated protein kinase (MAPK) family signaling cascade, and nuclear factor-kappaB pathway, whereas CCR4 affects the prognosis of OS by regulating eukaryotic translation. CONCLUSION: CCL5, CCL8, CCR4, and CCR5 are potential prognostic markers for the prognosis of childhood OS, and the underlying molecular mechanisms of childhood OS have been identified.

Integrated miRNA-mRNA network revealing the key molecular characteristics of ossification of the posterior longitudinal ligament.

BACKGROUND: Ossification of the posterior longitudinal ligament (OPLL) refers to an ectopic ossification disease originating from the posterior longitudinal ligament of the spine. Pressing on the spinal cord or nerve roots can cause limb sensory and motor disorders, significantly reducing the patient's quality of life. At present, the pathogenesis of OPLL is still unclear. The purpose of this study is to integrate microRNA (miRNA)-mRNA biological information data to further analyze the important molecules in the pathogenesis of OPLL, so as to provide targets for future OPLL molecular therapy. METHODS: miRNA and mRNA expression profiles of GSE69787 were downloaded from Gene Expression Omnibus database and analyzed by edge R package. Funrich software was used to predict the target genes and transcription factors of de-miRNA. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of differentially expressed genes (DEGs) were carried out based on CLUEGO plug-in in Cytoscape. Using data collected from a search tool for the retrieval of interacting genes online database, a protein-protein interaction (PPI) network was constructed using Cytoscape. The hub gene selection and module analysis of PPI network were carried out by cytoHubba and molecular complex detection, plug-ins of Cytoscape software respectively. RESULTS: A total of 346 genes, including 247 up-regulated genes and 99 down-regulated genes were selected as DEGs. SP1 was identified as an upstream transcription factor of de-miRNAs. Notably, gene ontology enrichment analysis shows that up- and down-regulated DEGs are mainly involved in BP, such as skeletal structure morphogenesis, skeletal system development, and animal organ morphogenesis. Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that only WNT signaling pathway was associated with osteogenic differentiation. Lymphoid enhancer binding factor 1 and wingless-type MMTV integration site family member 2 Wingless-Type MMTV Integration site family member 2 were identified as hub genes, miR-520d-3p, miR-4782-3p, miR-6766-3p, and miR-199b-5p were identified as key miRNAs. In addition, 2 important network modules were obtained from PPI network. CONCLUSIONS: In this study, we established a potential miRNA-mRNA regulatory network associated with OPLL, revealing the key molecular mechanism of OPLL and providing targets for future treatment or prevent its occurrence.